How to take research to the next level?

1. How to take research to the next level? Michael Clark PhD

2. Research and audit? • Both involve answering specific questions which relate to the quality of care. • They can both be carried out either prospectively or retrospectively. • It is also true that both audit and research involve careful sampling, questionnaire design principles, and data collection and analysis • What is the difference? • http://www.leedsth.nhs.uk/sites/research_and_development/quick.php

3. Research • A structured activity which is intended to provide new knowledge which is generalisable (i.e. of value to others in a similar situation) and intended for wider dissemination • Department of Health 2002

4. Audit • A quality improvement process that seeks to improve patient care and outcomes through systematic review of care against explicit criteria and the implementation of change. Aspects of the structure, processes and outcomes of care are selected and systematically evaluated against explicit criteria. Where indicated, changes are implemented at an individual, team, or service level and further monitoring is used to confirm improvement in healthcare delivery • Principles for Best Practice in Clinical Audit, NICE, 2002

5. Still confused? • Research is about creating new knowledge, about whether new treatments work or whether some treatments are better than others. It determines what is best practice • Clinical audit is a way of finding out if we are doing what we should be doing. Are we following guidelines, and are we using best practice?

6. Common ground • Both audit and research involve answering a specific question relating to quality of care • Both can be carried out either prospectively or retrospectively • Both involve careful sampling, questionnaire design and analysis of findings • Both activities should be professionally led

7. Telling research from audit? • Research creates new knowledge about what works and what is best; clinical audit tells us if we are following best practice. • Research is based on a hypothesis; clinical audit measures against standards. • Research can involve patients trying an untested treatment method; clinical audit never involves patients trying new treatment methods. • Research may involve a degree of experimentation on patients; clinical audit never involves anything happening to the patient which is different to their normal treatment. • Research may involve allocating patients to different treatment groups; clinical audit never involves allocating patients to different treatment groups.

8. Telling research from audit? • Research may be based on a scientifically valid sample size; clinical audit sample sizes don't need to be scientifically valid. • Research may involve some detailed statistical analysis of the collected data; clinical audit requires only basic statistic analyses • The results from research are generalisable; clinical audit results are applicable within local settings only. • Research findings can have a wide reaching influence on clinical practice; clinical audit has a local influence on clinical practice but can be shared widely • Research involving NHS staff, patients, their tissue or data, or facilities and equipment requires ethics committee approval; clinical audit rarely requires ethics approval

9. Need both research and audit • Research can't survive without audit as we wouldn't know whether best practice was being carried out, and audit can't survive without research as without research we wouldn't know what best practice was • Research identifies areas for clinical audit and clinical audit identifies areas for research

10. Research or audit? • Answer these three questions – • Is the aim of your project to improve the quality of care for a particular patient group in the local setting (i.e. within the Trust)? YES • Will the project involve measuring practice against a set of standards? YES • Does your project involve anything being done to patients which is beyond what can be described as normal clinical management? NO

11. NO – NO – YES - Research • Where do you start? • Research governance framework for health and social care: Second edition • http://www.dh.gov.uk/en/publicationsandstatistics/publications/publicationspolicyandguidance/dh_4108962 • Research is essential to the successful promotion and protection of health and wellbeing, and also to modern, effective health and social care services. • At the same time, research can involve an element of risk, both in terms of return on investment and sometimes for the safety and wellbeing of the research participants. • Proper governance of research is essential to ensure that the public can have confidence in, and benefit from, quality research in health and social care. The public has a right to expect high scientific, ethical and financial standards, transparent decision making processes, clear allocation of responsibilities and robust monitoring arrangements

12. Research governance • The framework is of direct relevance to all those who host, conduct, participate in, fund and manage health and social care research. It is not just for investigators, managers or any one professional group. All service and academic staff, no matter how senior or junior, have a role to play in the conduct of research.

13. Research governance • The framework aims to forestall poor performance, adverse incidents, research misconduct and fraud, and to ensure that lessons are learned and shared when poor practice is identified. Learning from adverse events will promote good practice, enhance the ethical and scientific quality of research, and safeguard the public

14. Research governance • Standards across five domains • Ethics • Science • Information • Health, safety and employment • Finance and intellectual property • Read framework and its appendices for current standards and legislation

15. Science • All existing sources of evidence, especially systematic reviews, must be considered carefully before undertaking research. Research which duplicates other work unnecessarily, or which is not of sufficient quality to contribute something useful to existing knowledge, is unethical

16. Science • Every proposal for health and social care research must be subjected to (scientific) review by experts in the relevant fields able to offer independent advice on its quality . • Arrangements for peer review should be in proportion to the scale of the research and the risks involved • NHS R&D committees • Data collected in the course of research must be retained for an appropriate period, to allow further analysis by the original or other research teams subject to consent, and to support monitoring by regulatory and other authorities

17. Ethics • No research study within the NHS involving individuals, their organs, tissue or data may begin until it has a favourable opinion from a research ethics committee • Integrated Research Application System • https://www.myresearchproject.org.uk/ • Answer questions that compile both the ethics committee application and the NHS R&D application

18. Science and Ethics together • The principles of Good Clinical Practice apply to all research involving patients, not just clinical trials. • GCP is an international ethical and scientific quality standard for the design, conduct and record of research involving humans. • Comprised of 13 core principles, GCP applies to all clinical investigations that could affect the safety and well-being of human participants (in particular, clinical trials of medicinal products). • GCP was developed by the regulatory authorities of the EU, Japan and US in a steering group termed the Tripartite International Conference on Harmonisation (ICH) and provides international assurance that: • Data and reported results of clinical investigations are credible and accurate, and • Rights, safety and confidentiality of participants in clinical research are respected and protected

19. Good Clinical Practice • Research should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s). • Before research is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual research participant and society. Research should be initiated and continued only if the anticipated benefits justify the risks.  • The rights, safety, and well-being of the research participants are the most important considerations and should prevail over interests of science and society.  • The available nonclinical and clinical information on an investigational product should be adequate to support the proposed research.

20. Good clinical practice • Research should be scientifically sound, and described in a clear, detailed protocol. • Research should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion. • The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.

21. Good clinical practice • Each individual involved in conducting research should be qualified by education, training, and experience to perform his or her respective task(s). • Freely given informed consent should be obtained from every subject prior to research participation. • All research information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification. • The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s). • Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.  • Systems with procedures that assure the quality of every aspect of the research should be implemented.

22. (Science and ethics) to information • All those conducting health and social care research must open their work to critical review through the accepted scientific and professional channels. Once established, findings must be made accessible to those participating and to all those who could benefit from them. This may be through publication and/or other means appropriate to the type of research • Successful commercial development often depends upon the protection of intellectual property or commercial confidentiality at critical points in the innovation process. The timing of the publication of research findings needs to take account of this.

23. Getting involved If we don’t want to be Dr Frankenstein or Igor what do we have to watch out for?

24. Getting involved? • Most academic research today is carried out with multi-professional teamwork with little scope for single investigators • Educational research – MSc/PhD guidance and support with academic supervisors – USE THEM! • Other likely areas of activity relate to commercial supported research of medical devices (beds, dressings, TNP, electro-stimulation - anything that isn’t a medicine).

25. Getting involved • What questions to ask? • 1. Is it research or audit? Clinical audit never involves patients trying new treatment methods. • 2. Look at the protocol. • Study title and chief investigator, sponsor • Introduction • Study methods and materials • Design, objectives, sample size, study population, inclusion and exclusion criteria, primary and secondary outcomes, study materials and labelling, study duration, study termination/withdrawal, end of study, data storage • Protocol modifications • Subject selection • Interventions to be administered • Adverse events • Monitoring • Quality control and quality assurance • Ethics • Data handling and record keeping • Final report • Records, reports and retention requirements

26. Getting involved? • 3. Write a protocol – chief investigator. Each individual involved in conducting research should be qualified by education, training, and experience to perform his or her respective task(s). Research governance framework sets out responsibilities for chief investigators, investigators and researchers. Work within your competency. • 4. Check intervention has a CE mark. If no CE mark the research must be submitted for approval to the Medicines and Healthcare Products Regulatory Agency by the company.

27. Getting involved? • 5. Submission to ethics and NHS R&D. Who is to undertake this? Submissions need to be signed by someone who can commit the trust to undertaking the study. • 6. Financial agreements. For commercial research in secondary care, agreements will be between the commercial sponsor and each NHS body accountable for the care of NHS patients participating in the trial. In primary care, these contracts will normally be between the commercial sponsor and General Practitioners or Practices. Agreements not with the individual. Protect valuable resources – ‘know how’ of NHS staff, access to NHS patients.

28. Getting involved? • 7. Agreement to publish or present the results must be in the agreement. • 8. Are the timescales realistic? Human nature to be over optimistic regarding how many subjects are available and can be recruited. • 9. Always bear in mind throughout the study Each individual involved in conducting research should be qualified by education, training, and experience to perform his or her respective task(s)

29. Conclusions • Research can be differentiated from audit • Research is governed by a substantial framework protecting patients and staff. • Work through the key steps when starting a new project. Be clear about your role and responsibilities – am I competent to do this? • Research is fun.